Parallel artificial membrane permeability platform, an alternative regulatory approach to identify barrier function, permeability and DMPK analysis in BCS classification

The absorption of drugs taken orally is greatly affected by membrane Permeability. Intestinal Permeability has traditionally been evaluated using cell culture methods such as Caco-2 and Madin-Darby Canine Kidney (MDCK). One predictive technique for determining how formulation may affect the oral bioavailability of drugs in humans is the Biopharmaceutical Classification System (BCS). When coupled with in vitro dissolution studies, the BCS can aid in forecasting how a product would perform in a living organism and create mechanistic models to back up formulation evaluations. At this time, biowaivers are only available for medications that are extremely soluble in water, such as BCS class I and III medications. Due to the absence of Permeability interpretation, in vitro dissolution testing is insufficient for predicting in vivo drug performance when examining medicines with poor solubility, namely BCS class II/IV medications. The Parallel Artificial Membrane Permeability Assay (PAMPA) assay has become more prominent in the field of early drug discovery due to its low cost, high throughput compared to the more labour-intensive and supporting new advanced methodology (NAM) for drug discovery. Absorption, distribution, metabolism, and elimination (ADME) tests at Tier I are conducted at the National Centre for Advancing Translational Sciences (NCATS) using PAMPA pH 5. Over the years, it was developed and equipped with variable lipid components ideal for mimicking the epithellilal/Skin and blood-brain barrier related plasma membrane composition. We have thoroughly analyzed the PAMPA development checkpoints and assay variations in our manuscript. We have also explained about the different types of PAMPA systems like for applications mimicking GIT, BBB, and skin. In the manuscript the working of PAMPA is also explained with its role in the Drug Metabolism and Pharmacokinetics (DMPK) studies.